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DNA promotes the activation of oxygen molecules by binuclear cobalt(II) compounds
www.elsevier.nl/locate/inoche Inorganic Chemistry Communications 2 (1999) 609–611
DNA promotes the activation of oxygen molecules by binuclear cobalt(II) compounds Yuzo Nishida a,*, Satoshi Nishino a, Li Li Guo a, Mami Kunita a, Hideaki Matsushima b, Tadashi Tokii b b
a Institute for Molecular Science, Okazaki 444-8585i, Japan Department of Chemistry, Faculty of Science and Engineering, Saga University, Saga 840-8502, Japan
Received 12 October 1999
Abstract We have observed that binuclear cobalt(II) compounds with H(HPTP), Co2(HPTP)(CH3COO)(ClO4)2 and Co2(HPTP)Cl(ClO4)2, react with oxygen molecules when DNA is present in the solution, cleaving the DNA (H(HPTP) denotes N,N,N9,N9-tetrakis(2-pyridylmethyl)1,3-diaminopropane-2-ol). q1999 Elsevier Science S.A. All rights reserved. Keywords: DNA cleavage; Oxygen activation by DNA; Binuclear cobalt(II) compound
During the past decades there has been an explosion in research efforts directed towards the isolation and evaluation of naturally occurring DNA cleaving agents and towards the design and synthesis of model compounds that can specifically recognize and cut DNA. The potential scope of the utility of these compounds ranges from the creation of synthetic restriction enzymes for the use of biologists to the development of chemotherapeutic agents that may be effective against a variety of neoplastic diseases. The bleomycins (BLM) are a family of glycopeptide-derived antibiotics, discovered by Umezawa and co-workers, which have been used clinically against certain malignant lymphomas and squamous cell carcinomas [1]. The therapeutic activity of BLM is generally believed to correlate with the ability of an ‘activeBLM’, which is derived from either the Fe(II)-BLM/O2 or Fe(III)-BLM/H2O2 system, to bind to and degrade DNA [1–3]. This means that Fe-BLM is a dangerous species for human beings, because it always contains an active oxygen species, although the active bleomycin is quickly bleached when the drug is activated outside of this target (DNA). The most desirable agent for clinical use should be one that cleaves DNA oxidatively through the production of an active oxygen species only when it reacts with DNA. Here we show that some binuclear cobalt(II) compounds with H(HPTP) (see below) [4] belong to this type of compound. * Corresponding author. Fax: q81 564 55 5245; e-mail: [email protected]
In this study we have prepared the binuclear Zn(II), Ni(II) and Co(II) compounds with H(HPTP): Zn2(HPTP)(CH3COO)(ClO4)2, Ni2(HPTP)(C6H5COO)1.5(PF6)1.5, Co2(HPTP)(CH3COO)(ClO4)2 and Co2(HPTP)Cl(ClO4)2. The corresponding iron(III) complex Fe2(HPTP)Cl4ClO4 has already been reported [5]. A crystal structure determination of the Zn(II) complex has shown that this complex is a binuclear Zn(II) complex bridged by an alkoxo-oxygen atom and acetate group (see Supplementary material). Electrospray mass spectrometry (see Fig. 1) has also revealed that the cobalt(II) compounds obtained in this study are of a binuclear structure with an alkoxo-bridge, as confirmed in the Zn(II) complex. We have already reported that the iron(III) complex with H(HPTP) gave no Form II and Form III DNA in the reaction with Form I DNA [5], indicating that this complex does not cleave DNA in the absence of hydrogen peroxide. Fig. 2 shows the electrophoresis of the solution when DNA (pBR322, supercoiled Form I) was treated with Co2(HPTP)(CH3COO)(ClO4)2 [6,7]; this demonstrates that the addition of the cobalt(II) complex has induced the cleavage of Form I DNA in the absence of hydrogen peroxide, because formation of Form II DNA was observed. No Form
1387-7003/99/$ - see front matter q1999 Elsevier Science S.A. All rights reserved. PII S 1 3 8 7 - 7 0 0 3 ( 9 9 ) 0 0 1 6 5 - 3
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Y. Nishida et al. / Inorganic Chemistry Communications 2 (1999) 609–611
Fig. 1. Electrospray mass spectra of the solutions (in acetonitrile). (A) Co2(HPTP)(CH3COO)(ClO4)2: signals around m/zs315 and 729 correspond to Co2(HPTP)(CH3COO)2q and Co2(HPTP)(CH3COO)ClO4q, respectively. (B) Zn2(HPTP)(CH3COO)(PF6)2: signals around m/zs322 and 743 correspond to Zn2(HPTP)(CH3COO)2q and Zn2(HPTP)ClO4(CH3COO)q, respectively.
Fig. 2. Supercoiled ds-DNA(pBR322) was incubated aerobically with Co2(HPTP)(CH3COO)(ClO4)2 for 1 h at 298 K. The concentrations of the cobalt(II) complex solutions were varied as follows: lane 1, DNA alone; lane 2, 1.0 mM cobalt(II) complex; lane 3, 0.5 mM cobalt(II) complex; lane 4, 0.25 mM cobalt(II) complex; lane 5, 0.1 mM cobalt(II) complex.
II and Form III DNA was detected when the corresponding Zn(II) and Ni(II) compounds were used under the same experimental conditions (see Supplementary material). The binuclear cobalt(II) compounds obtained in this study gave no spectral change when dissolved in the same solution as used for the DNA cleavage reaction, indicating that the cobalt(II) compound itself does not react with the oxygen molecule. This indicates that the cobalt(II) complex used in this study reacts with the oxygen molecule to activate it when DNA is present in the solution, cleaving the DNA (see Scheme 1); this behavior is very similar to that reported for binuclear iron(III) complexes which oxidize the substrate only when three components, a metal complex, substrate and oxygen molecule, are present simultaneously in the solution [8,9]. Future development of new DNA cleaving agents for clinical use should take into account the point of view described in this paper.
Friday Nov 19 01:20 PM
Scheme 1.
Supplementary material Further data concerning the Zn(II) and Ni(II) compounds are available from the author on request.
References [1] J. Stubbe, J.W. Kozarich, Chem. Rev. 87 (1987) 1107. [2] J.W. Sam, X.-J. Tang, J. Peisach, J. Am. Chem. Soc. 116 (1994) 5250. [3] W. Wu, D.E. Vanderwall, C.J. Turner, J.W. Kozarich, J. Stubbe, J. Am. Chem. Soc. 118 (1996) 1281.
StyleTag -- Journal: INOCHE (Inorganic Chemistry Communications)
Article: 303
Y. Nishida et al. / Inorganic Chemistry Communications 2 (1999) 609–611 [4] Y. Nishida, M. Nasu, T. Akamatsu, Z. Naturforsch. 47b (1992) 115. [5] S. Nishino, M. Kunita, T. Kobayashi, H. Matsushima, T. Tokii, Y. Nishida, Z. Naturforsch. 54b (1999) 1272. [6] In a typical run, an aqueous solution of the iron(III) complex (4 ml of 0.1–2.0 mmol dmy3), DNA (4 ml of 0.1 mg per ml) and tris buffer (2 ml of 0.1 mol dmy3, pHs7.8) were mixed and allowed to stand for 1 h at 258C. The solution was electrophorated on 0.9% agarose
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gel containing ethidium(3,8-diamino-5-ethyl-6-phenylphenanthridinium) bromide [7]. The bands were photographed with Polaroid 667 film. [7] D.A. Micklos, G.A. Freyer, DNA Science, Cold Spring Harbour Laboratory Press, New York, 1990. [8] Y. Nishida, K. Yamada, J. Chem. Soc., Dalton Trans. (1990) 3639. [9] Y. Nishida, M. Nasu, T. Akamatsu, J. Chem. Soc., Chem. Commun. (1992) 93.
StyleTag -- Journal: INOCHE (Inorganic Chemistry Communications)
Article: 303
DNA promotes the activation of oxygen molecules by binuclear cobalt(II) compounds Yuzo Nishida a,*, Satoshi Nishino a, Li Li Guo a, Mami Kunita a, Hideaki Matsushima b, Tadashi Tokii b b
a Institute for Molecular Science, Okazaki 444-8585i, Japan Department of Chemistry, Faculty of Science and Engineering, Saga University, Saga 840-8502, Japan
Received 12 October 1999
Abstract We have observed that binuclear cobalt(II) compounds with H(HPTP), Co2(HPTP)(CH3COO)(ClO4)2 and Co2(HPTP)Cl(ClO4)2, react with oxygen molecules when DNA is present in the solution, cleaving the DNA (H(HPTP) denotes N,N,N9,N9-tetrakis(2-pyridylmethyl)1,3-diaminopropane-2-ol). q1999 Elsevier Science S.A. All rights reserved. Keywords: DNA cleavage; Oxygen activation by DNA; Binuclear cobalt(II) compound
During the past decades there has been an explosion in research efforts directed towards the isolation and evaluation of naturally occurring DNA cleaving agents and towards the design and synthesis of model compounds that can specifically recognize and cut DNA. The potential scope of the utility of these compounds ranges from the creation of synthetic restriction enzymes for the use of biologists to the development of chemotherapeutic agents that may be effective against a variety of neoplastic diseases. The bleomycins (BLM) are a family of glycopeptide-derived antibiotics, discovered by Umezawa and co-workers, which have been used clinically against certain malignant lymphomas and squamous cell carcinomas [1]. The therapeutic activity of BLM is generally believed to correlate with the ability of an ‘activeBLM’, which is derived from either the Fe(II)-BLM/O2 or Fe(III)-BLM/H2O2 system, to bind to and degrade DNA [1–3]. This means that Fe-BLM is a dangerous species for human beings, because it always contains an active oxygen species, although the active bleomycin is quickly bleached when the drug is activated outside of this target (DNA). The most desirable agent for clinical use should be one that cleaves DNA oxidatively through the production of an active oxygen species only when it reacts with DNA. Here we show that some binuclear cobalt(II) compounds with H(HPTP) (see below) [4] belong to this type of compound. * Corresponding author. Fax: q81 564 55 5245; e-mail: [email protected]
In this study we have prepared the binuclear Zn(II), Ni(II) and Co(II) compounds with H(HPTP): Zn2(HPTP)(CH3COO)(ClO4)2, Ni2(HPTP)(C6H5COO)1.5(PF6)1.5, Co2(HPTP)(CH3COO)(ClO4)2 and Co2(HPTP)Cl(ClO4)2. The corresponding iron(III) complex Fe2(HPTP)Cl4ClO4 has already been reported [5]. A crystal structure determination of the Zn(II) complex has shown that this complex is a binuclear Zn(II) complex bridged by an alkoxo-oxygen atom and acetate group (see Supplementary material). Electrospray mass spectrometry (see Fig. 1) has also revealed that the cobalt(II) compounds obtained in this study are of a binuclear structure with an alkoxo-bridge, as confirmed in the Zn(II) complex. We have already reported that the iron(III) complex with H(HPTP) gave no Form II and Form III DNA in the reaction with Form I DNA [5], indicating that this complex does not cleave DNA in the absence of hydrogen peroxide. Fig. 2 shows the electrophoresis of the solution when DNA (pBR322, supercoiled Form I) was treated with Co2(HPTP)(CH3COO)(ClO4)2 [6,7]; this demonstrates that the addition of the cobalt(II) complex has induced the cleavage of Form I DNA in the absence of hydrogen peroxide, because formation of Form II DNA was observed. No Form
1387-7003/99/$ - see front matter q1999 Elsevier Science S.A. All rights reserved. PII S 1 3 8 7 - 7 0 0 3 ( 9 9 ) 0 0 1 6 5 - 3
Friday Nov 19 01:20 PM
StyleTag -- Journal: INOCHE (Inorganic Chemistry Communications)
Article: 303
610
Y. Nishida et al. / Inorganic Chemistry Communications 2 (1999) 609–611
Fig. 1. Electrospray mass spectra of the solutions (in acetonitrile). (A) Co2(HPTP)(CH3COO)(ClO4)2: signals around m/zs315 and 729 correspond to Co2(HPTP)(CH3COO)2q and Co2(HPTP)(CH3COO)ClO4q, respectively. (B) Zn2(HPTP)(CH3COO)(PF6)2: signals around m/zs322 and 743 correspond to Zn2(HPTP)(CH3COO)2q and Zn2(HPTP)ClO4(CH3COO)q, respectively.
Fig. 2. Supercoiled ds-DNA(pBR322) was incubated aerobically with Co2(HPTP)(CH3COO)(ClO4)2 for 1 h at 298 K. The concentrations of the cobalt(II) complex solutions were varied as follows: lane 1, DNA alone; lane 2, 1.0 mM cobalt(II) complex; lane 3, 0.5 mM cobalt(II) complex; lane 4, 0.25 mM cobalt(II) complex; lane 5, 0.1 mM cobalt(II) complex.
II and Form III DNA was detected when the corresponding Zn(II) and Ni(II) compounds were used under the same experimental conditions (see Supplementary material). The binuclear cobalt(II) compounds obtained in this study gave no spectral change when dissolved in the same solution as used for the DNA cleavage reaction, indicating that the cobalt(II) compound itself does not react with the oxygen molecule. This indicates that the cobalt(II) complex used in this study reacts with the oxygen molecule to activate it when DNA is present in the solution, cleaving the DNA (see Scheme 1); this behavior is very similar to that reported for binuclear iron(III) complexes which oxidize the substrate only when three components, a metal complex, substrate and oxygen molecule, are present simultaneously in the solution [8,9]. Future development of new DNA cleaving agents for clinical use should take into account the point of view described in this paper.
Friday Nov 19 01:20 PM
Scheme 1.
Supplementary material Further data concerning the Zn(II) and Ni(II) compounds are available from the author on request.
References [1] J. Stubbe, J.W. Kozarich, Chem. Rev. 87 (1987) 1107. [2] J.W. Sam, X.-J. Tang, J. Peisach, J. Am. Chem. Soc. 116 (1994) 5250. [3] W. Wu, D.E. Vanderwall, C.J. Turner, J.W. Kozarich, J. Stubbe, J. Am. Chem. Soc. 118 (1996) 1281.
StyleTag -- Journal: INOCHE (Inorganic Chemistry Communications)
Article: 303
Y. Nishida et al. / Inorganic Chemistry Communications 2 (1999) 609–611 [4] Y. Nishida, M. Nasu, T. Akamatsu, Z. Naturforsch. 47b (1992) 115. [5] S. Nishino, M. Kunita, T. Kobayashi, H. Matsushima, T. Tokii, Y. Nishida, Z. Naturforsch. 54b (1999) 1272. [6] In a typical run, an aqueous solution of the iron(III) complex (4 ml of 0.1–2.0 mmol dmy3), DNA (4 ml of 0.1 mg per ml) and tris buffer (2 ml of 0.1 mol dmy3, pHs7.8) were mixed and allowed to stand for 1 h at 258C. The solution was electrophorated on 0.9% agarose
Friday Nov 19 01:20 PM
611
gel containing ethidium(3,8-diamino-5-ethyl-6-phenylphenanthridinium) bromide [7]. The bands were photographed with Polaroid 667 film. [7] D.A. Micklos, G.A. Freyer, DNA Science, Cold Spring Harbour Laboratory Press, New York, 1990. [8] Y. Nishida, K. Yamada, J. Chem. Soc., Dalton Trans. (1990) 3639. [9] Y. Nishida, M. Nasu, T. Akamatsu, J. Chem. Soc., Chem. Commun. (1992) 93.
StyleTag -- Journal: INOCHE (Inorganic Chemistry Communications)
Article: 303